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Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease
Alpha-synuclein (α-syn) is biochemically and genetically linked to Parkinson’s disease (PD) and other synucleinopathies. It is now widely accepted that α-syn can be released in the extracellular space, even though the mechanism of its release is still unclear. In addition, pathology-related aggregat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794345/ https://www.ncbi.nlm.nih.gov/pubmed/31649506 http://dx.doi.org/10.3389/fnmol.2019.00237 |
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author | Leandrou, Emmanouela Emmanouilidou, Evangelia Vekrellis, Kostas |
author_facet | Leandrou, Emmanouela Emmanouilidou, Evangelia Vekrellis, Kostas |
author_sort | Leandrou, Emmanouela |
collection | PubMed |
description | Alpha-synuclein (α-syn) is biochemically and genetically linked to Parkinson’s disease (PD) and other synucleinopathies. It is now widely accepted that α-syn can be released in the extracellular space, even though the mechanism of its release is still unclear. In addition, pathology-related aggregated species of α-syn have been shown to propagate between neurons in synaptically connected areas of the brain thereby assisting the spreading of pathology in healthy neighboring neuronal cells. In neurons, calcium channels are key signaling elements that modulate the release of bioactive molecules (hormones, proteins, and neurotransmitters) through calcium sensing. Such calcium sensing activity is determined by the distinct biophysical and pharmacological properties and the ability of calcium channels to interact with other modulatory proteins. Although the function of extracellular α-syn is currently unknown, previous work suggested the presence of a calcium-dependent mechanism for α-syn secretion both in vitro, in neuronal cells in culture, and also in vivo, in the context of a trans-neuronal network in brain. Mechanisms regulating extracellular α-syn levels may be of particular importance as they could represent novel therapeutic targets. We discuss here how calcium channel activity may contribute to α-syn aggregation and secretion as a pathway to disease progression in synucleinopathies. |
format | Online Article Text |
id | pubmed-6794345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67943452019-10-24 Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease Leandrou, Emmanouela Emmanouilidou, Evangelia Vekrellis, Kostas Front Mol Neurosci Neuroscience Alpha-synuclein (α-syn) is biochemically and genetically linked to Parkinson’s disease (PD) and other synucleinopathies. It is now widely accepted that α-syn can be released in the extracellular space, even though the mechanism of its release is still unclear. In addition, pathology-related aggregated species of α-syn have been shown to propagate between neurons in synaptically connected areas of the brain thereby assisting the spreading of pathology in healthy neighboring neuronal cells. In neurons, calcium channels are key signaling elements that modulate the release of bioactive molecules (hormones, proteins, and neurotransmitters) through calcium sensing. Such calcium sensing activity is determined by the distinct biophysical and pharmacological properties and the ability of calcium channels to interact with other modulatory proteins. Although the function of extracellular α-syn is currently unknown, previous work suggested the presence of a calcium-dependent mechanism for α-syn secretion both in vitro, in neuronal cells in culture, and also in vivo, in the context of a trans-neuronal network in brain. Mechanisms regulating extracellular α-syn levels may be of particular importance as they could represent novel therapeutic targets. We discuss here how calcium channel activity may contribute to α-syn aggregation and secretion as a pathway to disease progression in synucleinopathies. Frontiers Media S.A. 2019-10-09 /pmc/articles/PMC6794345/ /pubmed/31649506 http://dx.doi.org/10.3389/fnmol.2019.00237 Text en Copyright © 2019 Leandrou, Emmanouilidou and Vekrellis. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Leandrou, Emmanouela Emmanouilidou, Evangelia Vekrellis, Kostas Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease |
title | Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease |
title_full | Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease |
title_fullStr | Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease |
title_full_unstemmed | Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease |
title_short | Voltage-Gated Calcium Channels and α-Synuclein: Implications in Parkinson’s Disease |
title_sort | voltage-gated calcium channels and α-synuclein: implications in parkinson’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794345/ https://www.ncbi.nlm.nih.gov/pubmed/31649506 http://dx.doi.org/10.3389/fnmol.2019.00237 |
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